This application is a continuation of U.S. Ser. No. 15/989,738 filed May 25, 2018, which is a divisional of U.S. Ser. No. 13/779,511 filed Feb. 27, 2013, now U.S. Pat. No. 10,004,703, which is a continuation of U.S. Ser. No. 12/444,908, filed Apr. 9, 2009, now abandoned, which is a national phase application claiming priority under 35 U.S.C. § 120 from PCT/USN/081128 filed on Oct. 11, 2007, and claims the benefit, under 35 U.S.C. § 119(e), of U.S. Provisional Application 60/851,412 filed Oct. 12, 2006 , the entire disclosures of which applications are hereby incorporated by reference in their entireties.
Sulfonylurea drugs and related drugs are believed to act on the type 1 sulfonylurea receptor (SUR1 receptor) and the type 2 sulfonylurea receptor (SUR2). Sulfonylurea drugs have been shown to be effective in treating stroke and spinal cord injury due to the drug acting on a non selective cation channel which has type 1 sulfonylurea receptor (SUR1) binding sites and thus binds to Sulfonylureas. This channel is a non-selective Ca++-activated ATP-sensitive cation channel termed the “NCCa-ATP channel” (see, e.g., Chen and Simard, Journal of Neuroscience 21:6512-6521 (2001); and Chen et al., Journal of Neuroscience 23; 8568-8577 (2003), each hereby incorporated by reference) and is believed to include a regulatory sub-unit including a SUR1 receptor, and a pore subunit that has similar properties to, and may be comprised of, a TRPM4 channel (see, e.g., Simard et al., Biochimica et Biophysica Acta, 1772(8):947-957 (2007), hereby incorporated by reference). There is also some ex-vivo evidence that certain Sulfonylureas may have an effect in treating Parkinson's disease, and the KATP channel has been implicated in this regard.
There have been numerous studies as to the association between Alzheimer's disease (AD) and Type 2 Diabetes. Type 2 Diabetes has been found to be both negatively and positively associated with AD. Thus, according to the scientific literature, the relationship, if any, between Type 2 Diabetes and AD remains unknown.
Dementia is a term describing loss of mental function in a patient. As used herein, the term “dementia” refers to broadly to a psychiatric or medical condition characterized by cognitive deficits that may include impairments in memory, reasoning, planning, and judgment. Senile dementia is a dementia having an onset at an advanced age. One form of dementia that is more frequent in aged than in younger individuals is multi-infarct dementia, characterized by brain damage resulting from multiple infarcts, or strokes. Other forms of brain injury, brain trauma, inflammation, or other insult to the brain may lead to or exacerbate dementia. Another form of dementia, Alzheimer's Disease (AD), is a particularly prevalent form of dementia, and is more frequently found in aged than in younger individuals.
AD is the most common form of dementia among older people, and initially involves the parts of the brain that control thought, memory, and language. There are classic histolopathologic findings in AD such as neurofibrillary tangles, neuritic (senile) plaques, Hirano bodies, granulovacuolar bodies of Simchowicz, Pick bodies and Lewy bodies. Many of these histopathologic findings are associated with neuronal cell death which occurs insidiously many years before symptoms manifest.